This proposal is a detailed investigation of the neurophysiological and anatomical substrates of centrifugal control of sensory input to the primary somatosensory (SI) cortex. Preliminary experiments have shown a phasic, selective gating of cutaneous sensory input from the forepaw to single cells in the SI cortex of awake, freely moving rats during treadmill locomotion. The effect of this modulation was to allow some cells to selectively respond only to the touch of the paw on the ground during the footfall phase of the forelimb step cycle. The responsiveness of other cells was blocked during footfall but many did respond to natural or electrical stimulation of the paw during the swing phase. The experiments proposed here are designed to help determine the anatomical site and also the source of this gating. First, the experiments already completed in the SI cortex will be extended to inlude single unit recordings in the cuneate nucleus (CN) and the ventrobasal (VB) thalamus of a wake rats. Stimulating electrodes will be implanted in the paw and used to directly test modulation of sensory transmission to these major relays to the SI cortex. Initial experiments map the sensory representation of the body in the VB and CN and also quantitatively define the receptive field properties of cells in these areas. Preliminary neuroanatomical studies using retrograde transport of horseradish peroxidase (HRP) have confirmed that the primary motor cortex (MI) projects heavily to the CNand also the SI cortex itself. To test if these projections could be responsible for the sensory gating described above, four studies will be performed. First, the topography of these MI cortical projections defined more precisely by enhanced localization of HRP labeling. Next, MI cortical areas in anesthetized animals will be electrically stimulated to test modulation of transmission into cells in the CN, VB, or the SI evoked by stimulation of lower centers. If certain MI cortical areas are found to reproducibly support such sensory modulation, the chronic unit experiments described above will be again carried out in rats in which these areas are lesioned. Finally, precise correlations will be made between the time course of activation of single cells in these MI cortical areas during locomotion and the time course of the phasic modulation.